Extrinsic and intrinsic factors regulating commensal-specific T helper-17 cells

调节共生特异性 T 辅助细胞 17 细胞的外在和内在因素

• 批准号: 9169816
• 负责人: Bei Liu
• 金额: $ 52.33万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-21 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9169816
• 关键词: Address; Adopted; Affinity; Antibodies; Antigen-Presenting Cells; Antigens; Autoimmune Diseases; Autoimmune Process; Automobile Driving; Bacteria; Bacterial Antigens; Bioinformatics; Biological Assay; Biometry; CD4 Positive T Lymphocytes; Cell Differentiation process; Cells; Cues; Data; Dendritic Cells; Development; Disease; Effector Cell; Etiology; Generations; Genetic; Genetic study; Gnotobiotic; Goals; Gram-Positive Rods; Health; Hybridomas; Immune; Immunity; Immunology; Immunophenotyping; In Vitro; Inflammatory; Interleukin-1 beta; Interleukin-6; Intervention; Intestines; Intrinsic factor; Laboratories; Lead; Light; Listeria; Listeria monocytogenes; Maps; Mediating; Mucosal Immune Responses; Mucous Membrane; Mus; Organism; Play; Process; Property; Publishing; Reporting; Research; Role; STAT3 gene; Signal Pathway; Signal Transduction; Small Intestines; Specificity; Surface; System; T cell differentiation; T cell response; T-Cell Receptor; T-Lymphocyte; Testing; Thinking; Transgenic Mice; Transgenic Organisms; base; cancer immunotherapy; commensal microbes; cytokine; experience; gastrointestinal; genetic approach; gut microbiota; in vivo; insight; interleukin-23; microbial; microbial colonization; mouse model; novel; prevent; response; success; tool

Project Summary   It is now widely appreciated that gut commensal bacteria play a major role in health and disease. While dysregulation of the intestinal flora has been shown to contribute to many autoimmune abnormalities, specific relationships between particular microbial species and the state of host immunity have been unraveled for only a small number of organisms. Recent studies have supported the notion that segmented filamentous bacterium is a key gut commensal bacterium for driving mucosal Th17 responses, which is arguably one of the most exciting discoveries in the field. However, there exist intense debates on key aspects of the development of mucosal Th17 cells. Taking advantage of unique tools recently developed, we aim to address three important questions: (1) Which cytokines are required for SFB-specific Th17 cell induction; (2) What are the specific mucosal APC subsets that present bacterial antigens; and (3) How does antigen affinity of TCRs impact on Th17 differentiation. The feasibility of this proposal is supported by (1) many unique tools that we developed, including CD4 T cell hybridomas, novel TCR transgenic mice and transgenic Listeria monocytogenes; and (2) our first-hand experience in mucosal immunology in general and with this experimental system in particular. Insights to be derived from this project will be important for understanding and harnessing mucosal immune responses.

项目总结